This proposal is a request of continued support for preclinical psychopharmacology at the Tennessee Neuropsychiatric Institute. The research activities focus on (1) Pre- and postsynaptic catecholaminergic regulatory processes in the CNS and their modification by various psychotropic drugs (2) Studies on amine involvement in subserving the reinforcing and motivational properties of electrostimulation in specific brain areas and its modification by psychotropic drugs and (3) Basic enzymatic mechanisms for the metabolic inactivation of psychotropic drugs. In all three areas, special attention will be focused upon the development of new methodology to investigate the physiological and biochemical aspects of brain function. BIBLIOGRAPHIC REFERENCES: Blumberg, J.B., Vetulani, J., Stawarz, R.J. and Sulser, F., The noradrenergic cyclic AMP generating system in the limbic forebrain: Pharmacological characterization and possible role in the mode of action of antipsychotics. Europ. J. Pharmacol. 37, 357-366, 1976. Vetulani, J., Stawarz, R.J., Dingell, J.V., and Sulser, F., A possible common mechanism of action of antidepressant treatments: Reduction in the sensitivity of the noradrenergic cyclic AMP generating system in the rat limbic forebrain. Naunyn-Schmiedeberg's Arch. Pharmacol., 293, 109-114, 1976.